A kind of 2- (1- phenethyl) quinazolinone and its process for catalytic synthesis
Technical field
The invention provides a kind of quinazolinones and its synthetic method, relate more particularly to a kind of 2- (1- benzene second
Base) quinazolinone and its process for catalytic synthesis, belong to organic chemical synthesis field.
Background technology
Quinazolinone, can be as the structure fragment of active medicine, multiple used as the important nitrogen-containing heterocycle compound of a class
Concrete application field such as medicine, pesticide and chemical field have a wide range of applications.
At present, many quinazolinones medicines are widely used in actual life, have breast what Britain listed first
Treatment late period colorectal cancer medicine Raltitrexed (ralitrexed) of thuja acid synzyme (ts) inhibitory action, antitussive and antiasthmatic
Medicine, antiallergic agent tiacrilast (tiacrilast), act on the wide position of the upper maincenter of spinal cord, and make muscle tone
The muscle relaxant afloqualone (afloqualone) that hyperfunction state is alleviated;Sedative hypnotic mecloqualone (mecloqualone)
Deng.
In addition to above-mentioned application, ethamine dormancy ketone (etaqualone) of Quinazolinone-containing skeleton has stronger deinsectization effect,
It is used for acaricide to introduce to the market.And quinazolinone analog derivative also can be modified after modification and can be used for making herbicide, such as
Commercial herbicides bentazone is by the thio 2- position carbon for quinazolinone heterocyclic skeleton, therefore, also has in pesticide industry
It is widely applied.
As can be seen here, Quinazol derivative has wide application prospect.Just because of their excellent properties and
Great potential, scientists synthesize to it and have carried out substantial amounts of research, develop multiple synthetic methods and route in recent years.
K.siva kumar et al. (" a new cascade reaction:concurrent construction of
six and five membered rings leading to novel fused quinazolinones”,organic&
Biomolecular chemistry, 2012,10,3098-3103) in disclose isatic acid compound anhydride and r-nh-nh2Instead
Answer and quinazolinone benzindole class compound is obtained, wherein using pd (pph3) it is catalyst, binap is part.
Dong-sheng chen et al. (" copper (i)-catalyzed synthesis of 5-aryli dazolo
[3,2-b]quinazolin-7(5h)-one via ullman-type reaction”,the journal organic
Chemistry, 2013,78,5700-5704) disclose with 2- amino-n '-aryl phenylhydrazide and o- halogenated benzaldehyde in cubr
React with the presence of cesium carbonate, obtain 5- arylindazoles simultaneously [3,2-b] quinazoline -7- (5h) -one.
Weiguang, yang et al. (" copper-catalyzed intramolecular c-n bond formation
reaction of 3-amino-2-(2-bromophenyl)dihydroquinazolinon–es:synthesis of
Indazolo [3,2-b] quinazolinones ", tetrahedron, 2013,69,9852-9856) disclose 3- amino -2-
(2- bromophenyl) dihydroquinazoline ketone with copper compound/l- proline as catalyst, in the presence of cesium carbonate in nitrogen atmosphere
React, and obtain quinazolinone indazole compound.
The cn201310717678.7 of the applicant discloses the quinazolinone not using halogenide indazole derivative
Synthetic method, methods described is using palladium compound as catalyst, in the presence of alkali and molecular sieve, in oxygen atmosphere, formula
(ii) there is intramolecular dehydrogenation coupling reaction in compound, thus obtaining formula (i) derivant:
The cn 201410164235.4 of the applicant discloses the synthetic method of a kind of quinazolinone indazole derivative,
Using palladium compound as catalyst, in the presence of an oxidizer, in acidic organic solvent, formula (ii) compound methods described occurs
Intramolecular dehydrogenation coupling reaction, thus obtaining formula (i) derivant:
As described above, have been disclosed for multiple synthetic methods of Quinazol derivative in prior art, but for development
The synthetic method of new quinazolinones, still suffers from necessity, this basis that also exactly the present invention is accomplished and power institute
?.
Content of the invention
In order to seek quinazolinones and its synthetic method, present inventor has performed in-depth study, paying
After substantial amounts of creative work, thus completing the present invention.
Here, applicant is intended to illustrate, the technical scheme is that (project is criticized in Zhejiang Province's Natural Science Fund In The Light
Accurate number: be accomplished under subsidy ly14b020009), here is expressed thanks.
Specifically, technical scheme and content are related to 2- (1- phenethyl) quinazolinone and its side of catalyzing and synthesizing
Method.
More particularly it relates to quinazolinones shown in a kind of following formula (i), its structural formula is as follows:
Its chemical name is 2- (1- phenethyl) quinazolinone.
Second aspect, the present invention relates to quinazolinones shown in above formula (i), i.e. 2- (1- phenethyl) quinazolinone
Process for catalytic synthesis, methods described includes: in the presence of palladium catalyst, oxidant and alkali, following formula (ii) compound and n,
N- dimethylformamide (dmf) stirring sealing reaction, thus obtaining described formula (i) compound,
In the described process for catalytic synthesis of the present invention, described palladium catalyst is acid chloride (pd (oac)2), Palladous chloride.
(pdcl2), tetrakis triphenylphosphine palladium (pd (pph3)4), palladium acetylacetonate (pd (acac)2), palladium trifluoroacetate (pd (tfa)2), four
Ammino Palladous chloride. (pd (nh3)4cl2), two (triphenylphosphine) Palladous chloride. (pdcl2(pph3)2) or two pyridine Palladous chloride. (pdcl2
(py)2) in any one, preferably acid chloride (pd (oac)2) or palladium acetylacetonate (pd (acac)2), most preferably acetic acid
Palladium (pd (oac)2).
In the described process for catalytic synthesis of the present invention, described oxidant is potassium peroxydisulfate (k2s2o8), copper trifluoromethanesulfcomposite
(cu(otf)2), copper chloride (cucl2), iodobenzene diacetate (phi (oac)2), silver acetate (agoac), sodium peroxydisulfate (na2s2o8)、
Ammonium persulfate. ((nh4)2s2o8), any one in dicyano benzoquinone (ddq) or benzoquinone (bq), preferably potassium peroxydisulfate
(k2s2o8), copper trifluoromethanesulfcomposite (cu (otf)2) or sodium peroxydisulfate (na2s2o8), most preferably potassium peroxydisulfate (k2s2o8).
In the described process for catalytic synthesis of the present invention, described alkali is Feldalat NM (meona), cesium carbonate (csco3), acetic acid
Sodium (naoac), potassium carbonate (k2co3), potassium phosphate (k3po4), sodium carbonate (na2co3), potassium tert-butoxide (t-buoh), sodium hydroxide
(naoh) any one or in Sodium ethylate (etona), preferably sodium acetate or Sodium ethylate, most preferably sodium acetate.
In the described process for catalytic synthesis of the present invention, described formula (ii) compound is 1 with the mol ratio of catalyst:
0.05-0.15, for example, can be 1:0.05,1:0.1 or 1:0.15.
In the described process for catalytic synthesis of the present invention, described formula (ii) compound is 1:2-4 with the mol ratio of oxidant,
Can be for example 1:2,1:3 or 1:4.
In the described process for catalytic synthesis of the present invention, described formula (ii) compound is 1:0.5-1.5 with the mol ratio of alkali,
Can be for example 1:0.5,1:1 or 1:1.5.
In the described process for catalytic synthesis of the present invention, by mM in terms of (mmol) described formula (ii) compound of counting with
The ratio of the dmf that milliliter (ml) is counted is 1:10-30, and that is, every 1 mM of meter (mmol) described formula (ii) compound uses 10-30 milliliter
(ml) dmf, for example, can be 1:10,1:15,1:20,1:25 or 1:30.
Wherein, dmf, both as reaction dissolvent, also serves as reacting smooth methylating reagent, so not only may be used
With easy operation, it is easy to reaction controlling, and post processing is able to further easy, thus being more convenient the behaviour of whole reaction
Make.
In the described process for catalytic synthesis of the present invention, reaction temperature be 80-120 DEG C, for example can for 80 DEG C, 100 DEG C or
120℃.
In the described process for catalytic synthesis of the present invention, the response time is 20-40 hour, for example can for 20 hours, 25 little
When, 30 hours, 35 hours or 40 hours.
In the methods described of the present invention, the post processing after reaction terminates can be crystallization, recrystallization, chromatography over CC, extraction
Any one of take etc. the combination of processing means or multiple processing means.As a kind of exemplary post processing means, for example
Can be: after reaction completely, reaction system is naturally cooled to room temperature, add the ethyl acetate of equal-volume ratio and saturated aqueous common salt
Mixed liquor, oscillation extraction 2-4 time, collected organic layer, drying, rotary evaporation concentrates, and obtains crude product, crude product is crossed 300-400
Mesh silica gel column chromatography, with ethyl acetate and petroleum ether mixed liquor as eluant, the volume of wherein ethyl acetate and petroleum ether
Ratio 1:5-10, thus obtain target product formula (i) compound.
In the described process for catalytic synthesis of the present invention, the synthetic method of formula (ii) compound as initiation material is such as
Under: in organic solvent, in the presence of alkali and reducing agent, following formula (iii) compound and formula (iv) compound are in noble gases atmosphere
Enclose lower stirring reaction, thus obtaining formula (ii) compound,
In the synthetic method of described formula (ii) compound, described alkali be sodium carbonate, sodium bicarbonate, potassium carbonate, Sodium ethylate,
Any one in potassium tert-butoxide, ethanolamine, isopropanolamine etc., most preferably sodium carbonate.
In the synthetic method of described formula (ii) compound, described reducing agent is sodium sulfite (nahso3), sulfurous acid
Sodium (na2so3), ferrous sulfate (feso4) or stannous chloride (sncl2) in any one, most preferably sodium sulfite
(nahso3).
In the synthetic method of described formula (ii) compound, described organic solvent is n, n- dimethylformamide (dmf), n,
Appointing in n- dimethyl acetylamide (dma), chlorobenzene, benzene, dimethylbenzene, dimethyl sulfoxide (dmso), n- methyl pyrrolidone (nmp)
Meaning is a kind of, most preferably n, n- dimethyl acetylamide (dma).
Wherein, the consumption of described organic solvent is not particularly limited, for example, can carry out for ease of reaction and control, with
And it is easy to the amount of post processing, those skilled in the art can reasonably be determined according to routine techniquess means and be selected.
In the synthetic method of described formula (ii) compound, described atmosphere of inert gases can be for example nitrogen atmosphere or argon
Atmosphere.
In the synthetic method of described formula (ii) compound, the ratio of described formula (iii) compound and formula (iv) compound is
1:2-4, for example, can be 1:2,1:3 or 1:4.
In the synthetic method of described formula (ii) compound, described formula (iii) compound is 1:1- with the mol ratio of alkali
1.5, can be for example 1:1,1:1.2,1:1.4 or 1:1.5.
In the synthetic method of described formula (ii) compound, described formula (iii) compound is 1 with the mol ratio of reducing agent:
1.5-2.5, for example, can be 1:1.5,1:2 or 1:2.5.
In the synthetic method of described formula (ii) compound, reaction temperature be 80-110 DEG C, for example can for 80 DEG C, 90 DEG C,
100 DEG C or 110 DEG C.
In the synthetic method of described formula (ii) compound, the response time is 8-12 hour, for example can for 8 hours, 10 little
When or 12 hours.
In the synthetic method of described formula (ii) compound, post processing after the completion of reaction, will particularly as follows: after reaction terminates
Reaction system is poured into water, and separates out solid, standing, precipitation, filters, washing, is dried, by drying solid ethyl alcohol recrystallization, from
And obtain described formula (ii) compound.
As described above, the invention provides formula (i) compound, and provide the synthetic method of this compound, described conjunction
One-tenth method passes through selection and the synergism of suitable catalyst, oxidant and alkali, thus can get formula (i) compound, reacts bar
Part is simple, achieves good yield, the preparation for such compound provides new synthetic route simultaneously, in industry and scientific research
On there are good using value and potentiality.
Specific embodiment
Below by specific embodiment, the present invention is described in detail, but the purposes of these exemplary embodiments and
Purpose is only used for enumerating the present invention, and not the real protection scope of the present invention is constituted with any type of any restriction, more non-general
Protection scope of the present invention is confined to this.
Preparation example 1
To in appropriate dma, add anthranilamide, hyacinthin, sodium carbonate and sodium sulfite, then nitrogen atmosphere
Under be warming up to 80 DEG C, and stirring reaction 12 hours at such a temperature;Wherein, anthranilamide and the mol ratio of hyacinthin are
The mol ratio of 1:2, anthranilamide and sodium carbonate is that the mol ratio of 1:1, anthranilamide and sodium sulfite is
1:1.5.
React after terminating, reaction system is poured into water, separate out solid, stand, precipitate, filter, wash, be dried, will do
Dry solid ethyl alcohol recrystallization, thus obtaining described formula (ii) compound for light yellow solid, fusing point is 254.8-255 DEG C,
Yield is 86.9%.
Preparation example 2
Reaction equation with preparation example 1, concrete operations is:
To in appropriate dma, add anthranilamide, hyacinthin, sodium carbonate and sodium sulfite, then nitrogen atmosphere
Under be warming up to 90 DEG C, and stirring reaction 10 hours at such a temperature;Wherein, anthranilamide and the mol ratio of hyacinthin are
The mol ratio of 1:3, anthranilamide and sodium carbonate is the mol ratio of 1:1.2, anthranilamide and sodium sulfite
For 1:2.
React after terminating, reaction system is poured into water, separate out solid, stand, precipitate, filter, wash, be dried, will do
Dry solid ethyl alcohol recrystallization, thus obtaining described formula (ii) compound for light yellow solid, fusing point is with preparation example 1, yield
For 85.6%.
Preparation example 3
Reaction equation with preparation example 1, concrete operations is:
To in appropriate dma, add anthranilamide, hyacinthin, sodium carbonate and sodium sulfite, then nitrogen atmosphere
Under be warming up to 100 DEG C, and stirring reaction 8 hours at such a temperature;Wherein, anthranilamide and the mol ratio of hyacinthin are
The mol ratio of 1:4, anthranilamide and sodium carbonate is the mol ratio of 1:1.5, anthranilamide and sodium sulfite
For 1:2.5.
React after terminating, reaction system is poured into water, separate out solid, stand, precipitate, filter, wash, be dried, will do
Dry solid ethyl alcohol recrystallization, thus obtaining described formula (ii) compound for light yellow solid, fusing point is with preparation example 1, yield
For 87.1%.
Preparation example 4
Reaction equation with preparation example 1, concrete operations is:
To in appropriate dma, add anthranilamide, hyacinthin, sodium carbonate and sodium sulfite, then nitrogen atmosphere
Under be warming up to 110 DEG C, and stirring reaction 9 hours at such a temperature;Wherein, anthranilamide and the mol ratio of hyacinthin are
The mol ratio of 1:2.5, anthranilamide and sodium carbonate is 1:1.1, anthranilamide and sodium sulfite mole
Than for 1:2.5.
React after terminating, reaction system is poured into water, separate out solid, stand, precipitate, filter, wash, be dried, will do
Dry solid ethyl alcohol recrystallization, thus obtaining described formula (ii) compound for light yellow solid, fusing point is with preparation example 1, yield
For 85.9%.
Contrast preparation example 1-24: the investigation of alkali
Contrast preparation example 1-4: except respectively the alkali in preparation example 1-4 being replaced with addition to sodium bicarbonate by sodium carbonate, Qi Tacao
Make all constant, and implement contrast preparation example 1-4.
Contrast preparation example 5-8: except replacing with addition to potassium carbonate by the alkali in preparation example 1-4 by sodium carbonate respectively, other operates
All constant, and implement contrast preparation example 5-8.
Contrast preparation example 9-12: except replacing with addition to Sodium ethylate by the alkali in preparation example 1-4 by sodium carbonate respectively, other operates
All constant, and implement contrast preparation example 9-12.
Contrast preparation example 13-16: except replacing with addition to potassium tert-butoxide by the alkali in preparation example 1-4 by sodium carbonate respectively, other
Operation is all constant, and implements contrast preparation example 13-16.
Contrast preparation example 17-20: except respectively the alkali in preparation example 1-4 being replaced with addition to ethanolamine by sodium carbonate, Qi Tacao
Make all constant, and implement contrast preparation example 17-20.
Contrast preparation example 21-24: except replacing with addition to isopropanolamine by the alkali in preparation example 1-4 by sodium carbonate respectively, other
Operation is all constant, and implements contrast preparation example 21-24.
Acquired results see table.
As can be seen here, the species of wherein alkali has appreciable impact to products collection efficiency, and wherein sodium carbonate has best effect,
Even very similar with sodium carbonate sodium bicarbonate or potassium carbonate, its yield also has significant reduction.
Contrast preparation example 25-36: the investigation of reducing agent
Contrast preparation example 25-28: except respectively the reducing agent in preparation example 1-4 being replaced with sodium sulfite by sodium sulfite
Outward, other operations are all constant, and implement contrast preparation example 25-28.
Contrast preparation example 29-32: except respectively the reducing agent in preparation example 1-4 being replaced with ferrous sulfate by sodium sulfite
Outward, other operations are all constant, and implement contrast preparation example 29-32.
Contrast preparation example 33-36: except respectively the reducing agent in preparation example 1-4 being replaced with stannous chloride by sodium sulfite
Outward, other operations are all constant, and implement contrast preparation example 33-36.
Acquired results see table.
As can be seen here, reducing agent species has appreciable impact to products collection efficiency, and wherein sodium sulfite has best effect
Really, even very similar with sodium sulfite sodium sulfite, its yield also has significant reduction.
Contrast preparation example 37-42: the investigation of solvent
Except solvent therein is replaced with by dma in addition to following solvent, with preparation example 1-4 identical mode and real respectively
Apply contrast preparation example 37-42, the yield of used solvent, preparation example corresponding relation and corresponding product is as shown in the table.
As can be seen here, solvent equally has certain impact to final result, and wherein dma has best effect, even if
It is the dmf very similar with it, the also decrease to some degree of its yield.
Embodiment 1
To in dmf, add above formula (ii) compound, acid chloride, potassium peroxydisulfate and sodium acetate, then heat to 80 DEG C, and
Stirring sealing reaction 40 hours at such a temperature;Wherein, formula (ii) compound and the mol ratio of acid chloride are 1:0.05, formula (ii)
The mol ratio of compound and potassium peroxydisulfate is the mol ratio of 1:2, formula (ii) compound and sodium acetate is 1:0.5, and with mmoles
You count the ratio of (mmol) described formula (ii) compound counted and dmf counting with milliliter (ml) as 1:10.
After reaction completely, reaction system is naturally cooled to room temperature, add ethyl acetate and the saturated common salt of equal-volume ratio
The mixed liquor of water, oscillation extraction 2-4 time, collected organic layer, drying, rotary evaporation concentrates, and obtains crude product, crude product is crossed 300-
400 mesh silica gel column chromatography, with ethyl acetate and petroleum ether mixed liquor as eluant, the body of wherein ethyl acetate and petroleum ether
Long-pending ratio 1:5, thus obtaining target product formula (i) compound, product is 92.3%.
Fusing point: 210-211 DEG C.
Nuclear magnetic resonance, NMR:1hnmr(500mhz,cdcl3) δ 9.53 (s, 1h), 8.24 (d, j=8.0hz, 1h), 7.78-7.76
(m,2h),7.49-7.46(m,1h),7.39-7.38(m,2h),7.36-7.33(m,2h),7.30-7.27(m,1h),4.16-
4.12 (m, 1h), 1.77 (d, j=7.0hz, 3h).
13cnmr(125mhz,cdcl3)δ162.7,157.7,149.2,140.7,134.8,129.4(2c),128.0,
127.9(2c),127.8,126.8,126.5,121.1,45.8,19.0.
Embodiment 2
Reaction equation with embodiment 1, concrete operations is:
To in dmf, add formula (ii) compound, acid chloride, potassium peroxydisulfate and sodium acetate, then heat to 100 DEG C, and
Stirring sealing reaction 30 hours at a temperature of being somebody's turn to do;Wherein, the mol ratio of formula (ii) compound and acid chloride is 1:0.1, formula (ii) changes
The mol ratio of compound and potassium peroxydisulfate is the mol ratio of 1:3, formula (ii) compound and sodium acetate is 1:1, and by mM in terms of
(mmol) ratio of described formula (ii) compound counted and the dmf being counted with milliliter (ml) is as 1:20.
After reaction completely, reaction system is naturally cooled to room temperature, add ethyl acetate and the saturated common salt of equal-volume ratio
The mixed liquor of water, oscillation extraction 2-4 time, collected organic layer, drying, rotary evaporation concentrates, and obtains crude product, crude product is crossed 300-
400 mesh silica gel column chromatography, with ethyl acetate and petroleum ether mixed liquor as eluant, the body of wherein ethyl acetate and petroleum ether
Long-pending ratio 1:10, thus obtaining target product formula (i) compound, product is 91.9%.
Fusing point and nuclear magnetic resonance data are with embodiment 1.
Embodiment 3
Reaction equation with embodiment 1, concrete operations is:
To in dmf, add formula (ii) compound, acid chloride, potassium peroxydisulfate and sodium acetate, then heat to 120 DEG C, and
Stirring sealing reaction 20 hours at a temperature of being somebody's turn to do;Wherein, the mol ratio of formula (ii) compound and acid chloride is 1:0.15, formula (ii) changes
The mol ratio of compound and potassium peroxydisulfate is the mol ratio of 1:4, formula (ii) compound and sodium acetate is 1:1.5, and with mM
The ratio counting (mmol) described formula (ii) compound counted and dmf counting with milliliter (ml) is as 1:30.
After reaction completely, reaction system is naturally cooled to room temperature, add ethyl acetate and the saturated common salt of equal-volume ratio
The mixed liquor of water, oscillation extraction 2-4 time, collected organic layer, drying, rotary evaporation concentrates, and obtains crude product, crude product is crossed 300-
400 mesh silica gel column chromatography, with ethyl acetate and petroleum ether mixed liquor as eluant, the body of wherein ethyl acetate and petroleum ether
Long-pending ratio 1:7, thus obtaining target product formula (i) compound, product is 93.2%.
Fusing point and nuclear magnetic resonance data are with embodiment 1.
Embodiment 4
Reaction equation with embodiment 1, concrete operations is:
To in dmf, add formula (ii) compound, acid chloride, potassium peroxydisulfate and sodium acetate, then heat to 90 DEG C, and
Stirring sealing reaction 25 hours at a temperature of being somebody's turn to do;Wherein, the mol ratio of formula (ii) compound and acid chloride is 1:0.08, formula (ii) changes
The mol ratio of compound and potassium peroxydisulfate is the mol ratio of 1:3.5, formula (ii) compound and sodium acetate is 1:0.9, and with mmoles
You count the ratio of (mmol) described formula (ii) compound counted and dmf counting with milliliter (ml) as 1:15.
After reaction completely, reaction system is naturally cooled to room temperature, add ethyl acetate and the saturated common salt of equal-volume ratio
The mixed liquor of water, oscillation extraction 2-4 time, collected organic layer, drying, rotary evaporation concentrates, and obtains crude product, crude product is crossed 300-
400 mesh silica gel column chromatography, with ethyl acetate and petroleum ether mixed liquor as eluant, the body of wherein ethyl acetate and petroleum ether
Long-pending ratio 1:9, thus obtaining target product formula (i) compound, product is 92.7%.
Fusing point and nuclear magnetic resonance data are with embodiment 1.
The investigation of comparative example 1-28: catalyst
Comparative example 1-4: except replacing with addition to Palladous chloride. by the catalyst in embodiment 1-4 by acid chloride respectively, other
Operation is all constant, and implements comparative example 1-4.
Comparative example 5-8: except respectively the catalyst in embodiment 1-4 being replaced with tetrakis triphenylphosphine palladium by acid chloride
Outward, other operations are all constant, and implement comparative example 5-8.
Comparative example 9-12: except respectively the catalyst in embodiment 1-4 being replaced with addition to palladium acetylacetonate by acid chloride,
Other operations are all constant, and implement comparative example 9-12.
Comparative example 13-16: except respectively the catalyst in embodiment 1-4 being replaced with palladium trifluoroacetate by acid chloride
Outward, other operations are all constant, and implement comparative example 13-16.
Comparative example 17-20: except respectively the catalyst in embodiment 1-4 being replaced with four ammino Palladous chloride .s by acid chloride
Outward, other operations are all constant, and implement comparative example 17-20.
Comparative example 21-24: except respectively the catalyst in embodiment 1-4 being replaced with two (triphenylphosphines) by acid chloride
Outside Palladous chloride., other operations are all constant, and implement comparative example 21-24.
Comparative example 25-28: except respectively the catalyst in embodiment 1-4 being replaced with two pyridine Palladous chloride .s by acid chloride
Outward, other operations are all constant, and implement comparative example 25-28.
Acquired results see table.
As can be seen here, the species of catalyst has appreciable impact, wherein acid chloride and palladium acetylacetonate to have on products collection efficiency
There is preferable catalytic effect, and acid chloride then has a best catalytic performance, even very similar with acid chloride trifluoro second
Sour palladium, its yield also drastically reduces to 4.7-6.8%, has had been out the value of practical application.
The investigation of comparative example 29-36: oxidant
Except oxidant therein is replaced with by potassium peroxydisulfate in addition to following oxidant, with embodiment 1-4 identical side
Formula and implement comparative example 29-36 respectively, the yield of used oxidant, embodiment corresponding relation and corresponding product is as follows
Shown in table.
As can be seen here, in all of oxidant, potassium peroxydisulfate (k2s2o8), copper trifluoromethanesulfcomposite (cu (otf)2) or mistake
Sodium sulfate (na2s2o8) there is good oxidation susceptibility, potassium peroxydisulfate then has best oxidation susceptibility;And other oxidant is then
Yield all significantly reduces, or even cannot obtain product.In addition it is also possible to find out, even very similar with potassium peroxydisulfate
Sodium peroxydisulfate, its oxidation effectiveness is also greatly reduced to 49.1%, and equally very similar with potassium peroxydisulfate Ammonium persulfate., then
There is significantly more reduction.
The investigation of comparative example 37-44: alkali
Except alkali therein is replaced with addition to following alkali by peracetic acid sodium, with embodiment 1-4 identical mode and difference
Implement comparative example 37-44, the yield of used alkali, embodiment corresponding relation and corresponding product is as shown in the table.
As can be seen here, when using other alkali, the equal decrease to some degree of products collection efficiency, wherein sodium acetate have best
Effect, and even very similar with sodium acetate sodium formate, its effect also significantly reduces.
In sum, can clearly be found out by above-mentioned all embodiments, when applying the method according to the invention, formula (ii) can be made
Compound is smoothly reacted with dmf, thus obtaining purpose product, and yield is good, post processing simple, the taking of these effects
, depend on the comprehensive synergism of Multiple factors such as catalyst, alkali and oxidant, when changing one factor of any of which all
Yield will be led to by significantly reducing.
It should be appreciated that the purposes of these embodiments is merely to illustrate the present invention and is not intended to limit the protection model of the present invention
Enclose.Additionally, it will also be appreciated that after the technology contents having read the present invention, those skilled in the art can make each to the present invention
Plant and change, change and/or modification, all these equivalent form of value equally falls within the guarantor that the application appended claims are limited
Within the scope of shield.